Abstract WP234: Early administration of andexanet alfa reduces hematoma expansion in factor Xa inhibitor-associated intracerebral hemorrhage

Background: Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors and has been available in Japan since May 2022. Data on the efficacy and safety of andexanet alfa in patients with intracerebral hemorrhage (ICH) taking factor Xa inhibitors (FXaI) is limited, especially regarding the association with time metrics. Objective: To evaluate the efficacy of Andexanet alfa in ICH patients taking FXaI. Methods: Patients taking FXaI within 24 hours of the ICH onset were included from our single-center prospective registry. We compared consecutive patients treated with andexanet alfa from May 2022 to March 2025 with a consecutive historical cohort managed without andexanet alfa from January 2019 to May 2022. Patients who were directly transferred to the operating room from the emergency department for emergent hematoma removal or ventriculostomy were excluded. We calculated hematoma volume on baseline and 24-hour non-contrast CT and evaluated hematoma expansion, defined as a 33% or 6.0mL or more increase from baseline. Functional outcome was assessed at 90 days, and the favorable outcome was defined as mRS score of 0-3 or the same as before onset. We collected data on time metrics and examined the association between the hematoma expansion or the favorable outcome and the onset-to-door (OTD) time. Results: A total of 72 patients (median age, 80 years; female, 27; median NIHSS score, 14) were included. Andexanet alfa was administered in 40 (56%) patients with the median door-to-needle time of 52 minutes. The median OTD time was shorter in the andexanet alfa group (112 vs 301 minutes, p=0.04)(Table). The initial hematoma volume does not differ between the two groups (11 vs 19 mL), but the hematoma expansion was significantly less observed in the andexanet alfa group adjusted by age and NIHSS score (28% vs 75%, adjusted odds ratio 0.12; 95%CI 0.04 – 0.37). This association tended to be consistent regardless of OTD time but was more pronounced in the patients with a shorter OTD time (Figure). The rate of favorable outcome was numerically higher in the andexanet alfa group but did not differ significantly between the two groups (53% vs 38%, adjusted odds ratio 2.45; 95%CI 0.89-6.72). Conclusions: Early administration of andexanet alfa inhibits hematoma expansion and might contribute to improved functional outcome in intracerebral hemorrhage patients associated with factor Xa inhibitors.